In this work, nonrobust (average yield) and robust (varying yield) optimization techniques were applied to find the minimum radius required from the center of Chicago, Illinois, United States (U.S.) and land area by type to meet the population's nutritional needs given yield data for conventional and urban agricultural products. Twenty-eight nutrients were considered, and land type availability was defined using satellite data. No mix of food items were able to satisfy the vitamin D, vitamin B12, and calcium needs within a radius up to 650 km. With vitamin D fortification, radii between 175 and 185 km (nonrobust) and 205 and 220 km (robust) were found across scenarios. The inclusion of urban agriculture reduced the radius by 10-15 km and increased the diversity of foods in the solution. When vitamin B12 was supplemented, the radii could be reduced to 105-120 km (nonrobust) and 115-130 km (robust). This work demonstrates the need to include a full list of nutrients when evaluating the feasibility of localizing food systems. Key nutrient fortification or supplementation may significantly reduce the land area required to meet the nutritional needs of a population.Hydride ligands of transition metal polyhydride complexes with a high coordination number are prone to fluxionality leading to interesting structural dynamics. However, the underlying polytopal rearrangement pathways have been rarely studied. Based on quantum chemical calculations carried out in this work with density functional theory and coupled-cluster theory, two new fluxional mechanisms have been identified for the rhenium polyhydride complex ReH5(PPh3)2(pyridine) to jointly account for two consecutive coalescence events in the variable-temperature NMR spectra upon heating lateral and basal three-arm turnstile rotation. The frequently cited pseudorotation in ReH5(PPh3)2(pyridine) (Lee et al. Inorg. Chem.1996,35, 695) turns out to be a three-step process including two lateral three-arm turnstile steps and one basal turnstile step in between. The new fluxional mechanisms discovered in this work may also exist in other transition metal polyhydrides.Organic phototransistors (OPTs) have attracted enormous attention because of their promising applications in sensing, communication, and imaging. Currently, most OPTs reported utilize field-effect transistors (FETs) with relative long channel length which usually has undesired amplification because of their inherent low transconductance originated from their low channel capacitance, limiting the further improvement of performance. Herein, a vertical channel hybrid electrochemical phototransistor with a nanoscale channel and large transconductance (VECPT) is invented for the first time to achieve ultrahigh photoresponsivity along with a fast response speed. Benefiting from the nanoscale channel length and large transconductance, the photo-generated carriers in channel can be efficiently dissociated, transported, and amplified into the enlarged photocurrent output. Therefore, the devices deliver substantially improved optoelectronic performances with a photoresponsivity as high as ?2.99 × 107 A/W, detectivity of ?1.49 × 1013 Jones, and fast-speed response of ?73 μs under a low voltage of 1 V, which are superior to those of the reported OPTs based on FETs. Moreover, the in situ Kelvin probe microscopy is performed to characterize the surface potential of device systems for better elucidating the photosensing mechanism. Furthermore, taking advantage of its excellent optoelectronic performance, an ultraviolet light monitoring system is constructed by integrating VECPT with a light-emitting diode, which also shows the real-time, high-sensitive, and controllable photoresponse threshold properties. All these results demonstrate the great potential of these electrochemical phototransistors and provide valuable insights into the design of the nanoscale channel length device system for high-performance photodetection.Peptides are being developed as targeted anticancer drugs to modulate cytosolic protein-protein interactions involved in cancer progression. However, their use as therapeutics is often limited by their low cell membrane permeation and/or inability to reach cytosolic targets. Conjugation to cell penetrating peptides has been successfully used to improve the cytosolic delivery of high affinity binder peptides, but cellular uptake does not always result in modulation of the targeted pathway. To overcome this limitation, we developed "angler peptides" by conjugating KD3, a noncell permeable but potent and specific peptide inhibitor of p53MDM2 and p53MDMX interactions, with a set of cyclic cell-penetrating peptides. https://www.selleckchem.com/products/cpi-613.html We examined their binding affinity for MDM2 and MDMX, the cell entry mechanism, and role in reactivation of the p53 pathway. We identified two angler peptides, cTAT-KD3 and cR10-KD3, able to activate the p53 pathway in cancer cells. cTAT-KD3 entered cells via endocytic pathways, escaped endosomes, and activated the p53 pathway in breast (MCF7), lung (A549), and colon (HCT116) cancer cell lines at concentrations in the range of 1-12 μM. cR10-KD3 reached the cytosol via direct membrane translocation and activated the p53 pathway at 1 μM in all the tested cell lines. Our work demonstrates that nonpermeable anticancer peptides can be delivered into the cytosol and inhibit intracellular cancer pathways when they are conjugated with stable cell penetrating peptides. The mechanistic studies suggest that direct translocation leads to less toxicity, higher cytosol delivery at lower concentrations, and lower dependencies on the membrane of the tested cell line than occurs for an endocytic pathway with endosomal escape. The angler strategy can rescue high affinity peptide binders identified from high throughput screening and convert them into targeted anticancer therapeutics, but investigation of their cellular uptake and cell death mechanisms is essential to confirming modulation of the targeted cancer pathways.Alzheimer's disease (AD) is associated with the aberrant self-assembly of amyloid-β (Aβ) protein into fibrillar deposits. The disaggregation of Aβ fibril is believed as one of the major therapeutic strategies for treating AD. Previous experimental studies reported that serotonin (Ser), one of the indoleamine neurotransmitters, and its derivative melatonin (Mel) are able to disassemble preformed Aβ fibrils. However, the fibril-disruption mechanisms are unclear. As the first step to understand the underlying mechanism, we investigated the interactions of Ser and Mel molecules with the LS-shaped Aβ42 protofibril by performing a total of nine individual 500 ns all-atom molecular dynamics (MD) simulations. The simulations demonstrate that both Ser and Mel molecules disrupt the local β-sheet structure, destroy the salt bridges between K28 side chain and A42 COO-, and consequently destabilize the global structure of Aβ42 protofibril. The Mel molecule exhibits a greater binding capacity than the Ser molecule. Intriguingly, we find that Ser and Mel molecules destabilize Aβ42 protofibril through different modes of action.